Drug Safety

Controlling your IBD with medications during pregnancy

If you've been diagnosed with IBD and are considering pregnancy, or are currently pregnant or breastfeeding, you might be thinking about the safety of your medications for your baby. Rest assured, we're here to help you understand how IBD drugs may impact your pregnancy so you can have the information you need as you prepare for the future.

Remember, talking with a doctor who specializes in the treatment of IBD during pregnancy is the best way to find out what's right for you.

Preeclampsia prevention with baby aspirin

Preeclampsia is a condition of high blood pressure during pregnancy that can cause injury to organs like your kidneys, liver, lungs and brain. Most often preeclampsia develops later in pregnancy (after week 20), but can also occur in the weeks following delivery. The most severe complication of preeclampsia is progression to eclampsia, which can result in seizures and may be life threatening. Several studies have shown that taking baby aspirin during pregnancy (either 81 mg [one a day] or 162 mg [2 a day]) starting in the first trimester can prevent the development of preterm preeclampsia and preterm delivery (delivery at or before week 34) in women who are at higher risk- this includes women with a history of autoimmune diseases like Crohn’s disease and ulcerative colitis. While patients with IBD are typically told to avoid non-steroidal anti-inflammatory (NSAID) medications, baby aspirin use has not been shown to increase the risk of IBD flares and is safe to take for preeclampsia prevention during pregnancy. It is recommended that baby aspirin be started between weeks 12 and 28 but ideally before week 16, and should be continued through delivery. Make sure to discuss this with your OBGYN and GI doctor at your early pregnancy visits.

IBD medications and safety considerations

5-ASA agents

5-ASA agents (mesalamine, balsalazide, sulfasalazine) are commonly used for mild to moderate ulcerative colitis and do not affect the immune system. They are safe to continue during pregnancy – as well as during breastfeeding – to treat symptoms and maintain remission. The one exception may be Asacol HD, which specifically contains a chemical in the coating of the tablet, not the drug itself, that has been linked to birth defects in rabbits. If you are taking Asacol HD and are planning a pregnancy or are pregnant, talk to your doctor about switching to another form.

Mesalamine also comes in rectal form (Canasa, which is a suppository, and Rowasa, which is an enema). Both are safe during pregnancy and breastfeeding.

Antibiotics

Many doctors use antibiotics to treat infections, pouchitis and some fistulas. We recommend avoiding ciprofloxacin, but instead using short courses of metronidazole (Flagyl) and Augmentin when necessary. For women who develop C. difficile infection, oral vancomycin is recommended.

If you need to take antibiotics for an infection unrelated to your IBD while pregnant, please make sure to discuss with your GI doctor. There are some antibiotics that are safe in pregnancy but higher risk in IBD patients, such as clindamycin, that should be avoided if possible.

Steroids

Budesonide is the generic for Entocort and UCERIS^®. This is used for less serious symptoms than those that require prednisone. It is unclear if budesonide is safer than prednisone during pregnancy, though overall it is considered to be a safer medication because it causes less immunosuppression and fewer side effects. Both budesonide and prednisone can be used to treat flares during pregnancy if needed. If your flare is severe, your doctor will often choose to prescribe prednisone as it’s stronger and controls active inflammation faster than budesonide. Your doctor should try to use the lowest dose of steroids possible to control the disease. If you need steroids for a long time or are not able to wean off steroids, your doctor should consider adding another medicine for your IBD to get your inflammation controlled (remember, it is active inflammation, not IBD medication, that increases your risk of complications during pregnancy). Both budesonide and prednisone can be taken during breastfeeding, though you might need to adjust the timing of nursing if you are taking more than 20mg per day of prednisone.

There are multiple different forms of rectal steroids (both suppositories and enemas). These include Anusol, Uceris foam, Cortifoam, and Cortenemas, among others. All are safe during pregnancy and breastfeeding and are excellent additions if you are experiencing urgency, rectal bleeding, or tenesmus despite your long term IBD medication.

Immunomodulators

Common immunomodulators include azathioprine, 6-MP, and methotrexate. In high doses, azathioprine and 6-MP are used to treat cancer and are associated with a high risk for birth defects when used during pregnancy. However, this is not the case with the dosages used to treat IBD. Methotrexate is the exception. It should be stopped at least three months, and preferably six months, before conception.

Both azathioprine and 6-MP cross the placenta starting in the first trimester. Several studies have shown that exposure to immunomodulators in utero is not associated with an increased risk of birth defects or developmental delays in the fetus. These medications are also considered safe during breastfeeding, though they do get into the breastmilk in very small amounts.

Often, immunomodulators are used in combination with an anti-TNF medication to treat IBD. If your IBD is very well controlled, your doctor may decide to stop the immunomodulator when you start planning for pregnancy. However, some patients need to continue combination therapy throughout pregnancy to keep their disease controlled. This is also considered safe. You should be aware that if your doctor stops your immunomodulator, you may need the dose or frequency of your anti-TNF medication to be adjusted to maintain a good level of the anti-TNF in your blood. An increase in dosing or frequency of anti-TNF medications does not increase the risks of side effects or impact the safety of the medicine during pregnancy.

Of note, while immunomodulators and anti-TNFs alone are not associated with increased risk to the fetus during pregnancy or after delivery, some studies have shown that using these medicines in combination increases the risk of infection in the baby’s first year of life. Nonetheless, this risk is thought to be outweighed by the risks associated with active inflammation during pregnancy, and we therefore recommend that combination therapy be continued during pregnancy if needed to keep IBD controlled.

Biologic Therapy (anti-TNFs, anti-integrins, anti-interleukins)

All biologic therapies do not start to cross the placenta until week 27 of pregnancy. Importantly, the baby’s organs, bones and other anatomic structures all develop much earlier in the pregnancy (in the first 10 weeks), before any of these medications can get into the fetus’s bloodstream. Many years of research have now demonstrated that exposure to biologics in utero is not associated with an increased risk of birth defects, developmental delays, or infection in the first year of life.

Anti-TNF agents

The biologics REMICADE^®, HUMIRA^®, CIMZIA^® and SIMPONI^® and their biosimilars (Reflexis, Avsola, Inflectra, Amjetiva, Cytelzo, and Hyrimoz) are all considered safe during pregnancy. In fact, many doctors may start a woman on an anti-TNF during pregnancy rather than use steroids to manage active disease. CIMZIA^® is unique in that it doesn't cross the placenta, so the infant isn't exposed to the therapy at all. However, because all the anti-TNF agents have been shown to be safe for mom and baby during pregnancy, your doctor shouldn't switch you to CIMZIA^® in anticipation of pregnancy if you’re already on a different anti-TNF that’s working for you. Research on infants exposed to anti-TNF therapies during pregnancy does not suggest any increased risk for birth defects, developmental abnormalities, or serious infections in the first year of life.

Anti-TNF drug levels in newborn infants take a few months to clear from the blood if a mother receives any medications after the beginning of the third trimester. This does not impact the baby’s susceptibility to infection or their vaccine schedule. Use is also fine during breastfeeding as it does not appear any of these agents are secreted into milk.

Anti-interleukins

STELARA^® is an FDA approved therapy for IBD. It works by blocking two pathways that cause inflammation: IL-12 and IL-23. As above, it crosses the placenta but is not associated with increased risks to the baby during or after pregnancy. STELARA^® is also safe during breastfeeding.

Three newer medications, SKYRIZI^®, OMVOH^®, and TREMFYA^®, have recently been approved for the treatment of IBD (SKYRIZI^® for both Crohn's and ulcerative colitis; OMVOH^® and TREMFYA^® for ulcerative colitis only). All these medicines work by blocking the IL-23 pathway. Because these medications are so new, we do not yet have information regarding their safety during pregnancy or breastfeeding in humans. In animal studies, very high doses of SKYRIZI^® (much higher than those given to humans) were associated with decreased fetal viability. However, because these medicines work so similarly to STELARA^®, many physicians believe their safety profiles are similar as well and are comfortable starting or continuing these medications during pregnancy and breastfeeding. If you are taking one of these medications, please discuss next steps with your GI provider.

Small Molecules (JAK Kinase inhibitors, anti-sphingosine-1-phosphates)

Small molecule medications are taken in pill form. These medications cross the placenta starting in the first trimester and are present in breastmilk. There is limited safety data for these medications during pregnancy and breastfeeding in humans. The only safety data we have is based on animal studies.

JAK Kinase Inhibitors

XELJANZ^® and RINVOQ^® are FDA approved therapies for IBD (XELJANZ^® for ulcerative colitis; RINVOQ^® for both ulcerative colitis and Crohn’s disease). Although safety data in humans is limited, both medications have been shown to cause problems with bone development early in pregnancy in animal studies, and XELJANZ^® has been associated with miscarriage (of note, animals were given doses much higher than those given to humans). If you are taking one of these medications prior to pregnancy, your GI provider should attempt to switch you to a pregnancy-safe medication, like a biologic, before you attempt to conceive. If this is not possible (for example, if your disease cannot be controlled on anything but a JAK inhibitor), a risk-benefit discussion with your GI provider and an MFM is warranted. Moreover, resuming use in the second trimester (after bone and organ development is complete) could also be considered.

Importantly, both XELJANZ^® and RINVOQ^® are cleared from the body within 1-4 days of stopping treatment, and thus a long waiting period between stopping medication and trying to conceive is not needed. At this time, experts recommend stopping these medications four weeks before trying to conceive. If you learn you are pregnant while taking either of these medications, speak with your GI doctor, OBGYN and/or MFM about next steps.

Because both XELJANZ^® and RINVOQ^® are present in breastmilk and their potential impact on the nursing infant is not known, neither medicine is considered safe during breastfeeding.

Anti-Sphingosine-1-Phosphates

ZEPOSIA^® and VELSIPITY^® are FDA approved medications for the treatment of ulcerative colitis. Both are relatively newer medications with limited safety data in humans. Data from animal studies have found these medications to be harmful to the developing fetus. However, limited data from humans who became pregnant on ZEPOSIA^® during clinical trials did not find an increased risk of miscarriage, preterm birth, or birth defects compared to the general population. Nonetheless, women are advised to stop these medications before trying to become pregnant (12 weeks for ZEPOSIA^®, 1-2 weeks for VELSIPITY^®). Both medications should be avoided during breastfeeding.

Maternal vaccines during pregnancy

The American College of Obstetricians and Gynecologists (ACOG) recommends that all pregnant women are vaccinated against COVID-19 and influenza. These vaccines can be safely received during any trimester of pregnancy. While some women may be worried about receiving either or both vaccines, it is important to know that becoming ill with COVID or influenza during pregnancy can be severe and even life threatening. Receiving these vaccines is essential to preventing unnecessary illness while carrying your baby.

All pregnant women are also recommended to receive the Tdap vaccine (tetanus, diphtheria and pertussis, also called the whooping cough vaccine) between weeks 27 and 36 of each pregnancy, as well as the RSV vaccine between weeks 32 and 36 of pregnancy (if at this stage between September and January, which is RSV season). All of these vaccines are safe to receive while taking any long-term IBD medication. If you are on prednisone, talk to your doctor about the right timing of receiving a vaccine.

Live vaccines: Live vaccines should not be taken during pregnancy, regardless of what medications you are taking for IBD. Although the shingles vaccine, called Shingrix, doesn't contain the live virus, it's recommended that pregnant people delay vaccination.